Risk of Mild Behavioral Impairment: the role of gender and APOE allele carrier status

Background Gender differences in dementia and dementia‐related neuropsychiatric symptoms are well described. Similarly, the Apolipoprotein E (APOE) ε4 allele is a well‐known predictor of Alzheimer’s disease. However, their impact on the clinical manifestation of Mild Behavioral Impairment (MBI) remains unclear. Using data from the Australian population‐based PATH Through Life Study we explored the associations between gender and APOE ε4 carrier status with MBI. We hypothesized that MBI likelihood would be greater in males and ε4 carriers. Method 1316 dementia‐free participants (48% female; aged 72‐79) were included. Gender was self‐reported (female/male). Participants were classified as APOE ε4+ if they carried at least one ε4 allele (APOE ε4/ε4, ε2/ε4, ε3/ε4). MBI was approximated using a previously published transformation algorithm, which utilizes items from the Neuropsychiatric Inventory assessed at a single study visit. Binomial logistic regression was used to examine the role of gender and APOE ε4 carrier status, and their interaction, on predicting MBI status, while controlling for self‐reported years of education. Result Of the 1316 participants, 339 (25.8%) were APOE ε4+ and 445 (34%) had MBI symptoms. A higher proportion of APOE ε4+ carriers (χ2 (1) = 5.99, p = .014) and men (χ2 (1) = 4.59, p = .032) were in the MBI group compared to the non‐MBI group. Binomial logistic regression showed APOE ε4 carrier status (OR = 1.58, 95% CI: 1.063‐2.344) and male gender (OR = 1.45, 95% CI: 1.093‐1.925) were associated with a greater likelihood of MBI. Male gender was also associated with a 2‐fold greater likelihood of having symptoms of the Decreased Motivation (OR = 2.08, 95% CI: 1.13‐3.86) and Impulse Dyscontrol (OR = 2.16, 95% CI: 1.54‐3.03) domains. No interaction effects were found between gender and APOE ε4 carrier status for MBI or any of its domains. Conclusion The current study found that in dementia‐free older adults both male gender and APOE ε4+ status increased the risk of having MBI. However, no cumulative/interaction effect between gender and APOE ε4 carrier status was found, suggesting that being both male and APOE ε4+ does not further increase the risk of MBI. These results provide novel and valuable insight into the connection between gender, APOE ε4 carrier status and MBI

Affective and emotional dysregulation as pre-dementia risk markers: exploring the mild behavioral impairment symptoms of depression, anxiety, irritability, and euphoria

Background: Affective and emotional symptoms such as depression, anxiety, euphoria, and irritability are common neuropsychiatric symptoms (NPS) in pre-dementia and cognitively normal older adults. They comprise a domain of Mild Behavioral Impairment (MBI), which describes their emergence in later life as an at-risk state for cognitive decline and dementia, and as a potential manifestation of prodromal dementia. This selective scoping review explores the epidemiology and neurobiological links between affective and emotional symptoms, and incident cognitive decline, focusing on recent literature in this expanding field of research. Methods: Existing literature in prodromal and dementia states was reviewed, focusing on epidemiology, and neurobiology. Search terms included: “mild cognitive impairment,” “dementia,” “prodromal dementia,” “preclinical dementia,” “Alzheimer's,” “depression,” “dysphoria,” “mania,” “euphoria,” “bipolar disorder,” and “irritability.” Results: Affective and emotional dysregulation are common in preclinical and prodromal dementia syndromes, often being harbingers of neurodegenerative change and progressive cognitive decline. Nosological constraints in distinguishing between pre-existing psychiatric symptomatology and later life acquired NPS limit historical data utility, but emerging research emphasizes the importance of addressing time frames between symptom onset and cognitive decline, and age of symptom onset. Conclusion: Affective symptoms are of prognostic utility, but interventions to prevent dementia syndromes are limited. Trials need to assess interventions targeting known dementia pathology, toward novel pathology, as well as using psychiatric medications. Research focusing explicitly on later life onset symptomatology will improve our understanding of the neurobiology of NPS and neurodegeneration, enrich the study sample, and inform observational and clinical trial design for prevention and treatment strategies

High "Normal" blood glucose is associated with decreased brain volume and cognitive performance in the 60s: the PATH through Life Study

Context:Type 2 diabetes is associated with cerebral atrophy, cognitive impairment and dementia. We recently showed higher glucose levels in the normal range not to be free of adverse effects and to be associated with greater hippocampal and amygdalar atrophy in older community-dwelling individuals free of diabetes.Objective:This study aimed to determine whether blood glucose levels in the normal range

Depressive symptoms as a barrier to engagement in physical activity in older adults with and without Alzheimer's disease.

ObjectivesPhysical activity shows promise for reduced risk of Alzheimer's disease (AD) and protection against cognitive decline among individuals with and without AD. Older adults face many barriers to adoption of physically active lifestyles and people with AD face even further challenges. Physical activity is a promising non-pharmacological approach to improve depressive symptoms, but little is known about the impact of depressive symptoms as a potential barrier to engagement in physical activity. The present study aimed to investigate depressive symptoms as a potential barrier for participation in physical activity across a range of dementia severity.MethodWe used longitudinal structural equation modelling to investigate the bi-directional relationship between depressive symptoms and physical activity in 594 older adults with and without AD over a 2 year longitudinal follow up. Participants ranged from no cognitive impairment to moderately severe AD.ResultsWe found that depressive symptoms predicted reduced engagement in subsequent physical activity, but physical activity did not predict subsequent reductions in depressive symptoms.ConclusionWe conclude that depressive symptoms may be an important barrier to engagement in physical activity that may be addressed in clinical practice and intervention research

Caregiver rating bias in mild cognitive impairment and mild Alzheimer's disease: impact of caregiver burden and depression on dyadic rating discrepancy across domains

ABSTRACT Background: Caregivers of individuals with dementia are biased in their rating of mental health measures of the care receiver. This study examines caregiver burden and depression as predictors of this bias for mild cognitive impairment and mild Alzheimer's disease in different domains. Methods: The sample consisted of 202 persons: 60 with mild cognitive impairment, 41 with mild Alzheimer's disease, and 101 caregivers. Discrepancy scores were calculated by subtracting the mean caregiver score from the respective mean patient score on the following assessment instruments: the Geriatric Depression Scale, Apathy Evaluation Scale, Bayer-Activities of Daily Living Scale, and Quality of Life-AD scale. Caregiver burden and depression were assessed by the Zarit Burden Interview and the Center for Epidemiologic Studies Depression Scale. Results: Intraclass correlation coefficients were low for apathy (0.38), daily functioning (0.38), and quality of life (0.30) and moderate for depression (0.49). These domains showed negative rating discrepancies, which indicates caregiver rating bias for all four domains. Regression analyses revealed that caregiver burden significantly contributed to explaining these discrepancies in the domains apathy, daily functioning, and quality of life. Conclusion: Caregiver rating bias can be attributed to caregiver burden. When caregiver burden is present, data based on caregiver ratings should therefore be interpreted with caution

Apathy as a determinant of health behaviors in older adults: Implications for dementia risk reduction

Abstract INTRODUCTION Long‐term improvements in physical inactivity and other behavioral risk factors are integral to dementia risk reduction; however, sustained behavior change is challenging. Apathy, depression, and fatigue may impact engagement in health behaviors, but their presentation overlaps. This study investigates whether these symptoms are differentially associated with multiple health behaviors. METHODS In 1037 community‐dwelling older adults without dementia (aged 70–90, 55% women), regression analyses examined apathy, depression, and fatigue as predictors of health behaviors (physical activity, diet, alcohol, smoking) and a behavioral risk index. RESULTS Apathy was associated with reduced physical activity and alcohol use, and one or multiple behavioral risk factors. No or inconsistent relations were found between depression or fatigue and health behaviors. DISCUSSION Apathy is relevant to multiple health behaviors and should be considered when designing health promotion for older adults, including interventions for dementia risk reduction. Findings highlight the importance of distinguishing apathy from comorbid symptoms. Highlights Novel theory‐based perspective on behavioural risk factors for dementia. Higher apathy predicted less physical activity and alcohol use, and increased odds of lifestyle risk factors. Depressive symptoms were not associated with any health behavior. Apathy may be a determinant of multiple health behaviors in older adults, distinct from depression and fatigue. Considering apathy in precision prevention of dementia appears warranted

Blood pressure, brain structure, and cognition: opposite associations in men and women

BACKGROUND Research on associations between blood pressure, brain structure, and cognitive function has produced somewhat inconsistent results. In part, this may be due to differences in age ranges studied and because of sex differences in physiology and/or exposure to risk factors, which may lead to different time course or patterns in cardiovascular disease progression. The aim of this study was to investigate the impact of sex on associations between blood pressure, regional cerebral volumes, and cognitive function in older individuals. METHODS In this cohort study, brachial blood pressure was measured twice at rest in 266 community-based individuals free of dementia aged 68–73 years who had also undergone a brain scan and a neuropsychological assessment. Associations between mean blood pressure (MAP), regional brain volumes, and cognition were investigated with voxel-wise regression analyses. RESULTS Positive associations between MAP and regional volumes were detected in men, whereas negative associations were found in women. Similarly, there were sex differences in the brain–volume cognition relationship, with a positive relationship between regional brain volumes associated with MAP in men and a negative relationship in women. CONCLUSIONS In this cohort of older individuals, higher MAP was associated with larger regional volume and better cognition in men, whereas opposite findings were demonstrated in women. These effects may be due to different lifetime risk exposure or because of physiological differences between men and women. Future studies investigating the relationship between blood pressure and brain structure or cognitive function should evaluate the potential for differential sex effects.The work was supported by the Dementia Collaborative Research Centres and the NHMRC of Australia grant No. 1002160. Nicolas Cherbuin and Kaarin Anstey are funded by ARC Fellowship No. 12010227 and NHMRC Fellowships No.1002560